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Samenvatting Microbes and Infection

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  • 3 april 2021
  • 6 april 2021
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hannahkersbergen
#A BRIEF INTRODUCTION TO MEDICAL MICROBIOLOGY

Medical microbiology: field that deals with the interaction of microorganism and their human host
- commensals (microbes that typically stay in/on our body) → forms the microbiome/microbiota
- pathogens → infectious diseases

SARS-CoV-2 causing COVID-19
- emerged in November 2019 in China
- bats most probable origin: they are a flying vessel for all kind of viruses → zoonosis: transmission of
virus from bats or other animals to a human host (virus caused by a zoonotic event)
- by March 2021: ~120 million confirmed cases (most probably there are many more)
~1.6 million deaths

Impact of infectious diseases in history
- Plague (Black Death), middle ages, >> 100 million
- Smallpox, 18th century, > 60 million in Europe
- Spanish Flue (specific type of influenza virus), 1918/19, > 40 million (one of the worst
epidemics/pandemics in history)

Global causes of death according to WHO
- among the top ten causes of death in 2016 there were 3 types of infectious diseases:
1. Lower respiratory infections
2. Diarrhoeal diseases
3. Tuberculosis
- in total more than 6 million people died from infectious diseases

Global causes of death per income group
- infectious diseases are not equally distributed over the world:
- in high income countries they take a relatively minor role BUT lower respiratory infections
are still on place 6 of the top 10 causes of deaths
- in low income countries there are 5 types of infectious diseases among the top 10 causes
of death, so they take still a very important role

Development of infectious diseases mortality
- the number, the incidence or prevalence of infectious
diseases have declined significantly in recent years
- in low-income countries the decline was particularly
impressive, and the same was true for the lower middle
income countries
- in upper-middle or high-income countries there was not so
much gain between 2000 and 2015

4 groups of pathogens that cause infectious diseases
1. Viruses
- are the smallest pathogens
- ‘obligate cellular parasites’: they cannot replicate outside
of a host cell, because they have to use all the metabolism
and mechanisms present in the host cell to replicate
- they cause damage, because an infected cell can die and
usually dies, but they also cause damage by the immune reaction (immunopathology)
- difficult to treat, because the viruses hide in cells and in order to treat you can also impose damage

,on the host cell Viruses
- virus infections can be prevented by Size 18-750 nm, most < 200 nm
vaccines quite effectively, but the Structure DNA or RNA genome enclosed by protein
spread can also be prevented by shell +/- lipid membrane
hygienic measures (e.g. social Lifestyle ‘obligate cellular parasites’
Pathogenesis Direct damage by virus, immune reaction
distancing)
Treatment Much improved in recent years, but still
2. Bacteria limited
- bacteria excrete toxins (exotoxins) Prevention Vaccines, hygiene
but they also harbour toxins in their
Bacteria
cell wall for example
Size Usually 1-20 μm but can be larger
- immune reaction contributes to the
Structure Prokaryotes (no nucleus); spheres, rods,
pathogenesis
spirals as single cells, chains, or clusters
- big problem with antibiotic Lifestyle Extracellular or intracellular
resistance → evermore bacteria Pathogenesis Bacterial toxins, immune reaction
species get resistant to the antibiotics Treatment Antibiotics; problem antibiotic resistance
we have (very big problem currently) Prevention Vaccines, hygiene
3. Fungi
- can produce spores Fungi
- often don’t cause infections (or at Size Usually 3-5 μm but can be larger
least not clinically apparent infections Structure Eukaryotes; unicellular (yeast) or
in healthy individuals), but in people multicellular-filamentous (molds)
with a weakened immune system Lifestyle Replicate by budding, fission and/or via
they can cause quite devastating spores
infections (opportunistic infections) Pathogenesis Often opportunistic infections;
- because they are eukaryotes their immunopathology
metabolism is pretty close to the Treatment Possible but difficult due to toxicity
metabolism of our own cells → Prevention Hygiene, good health
treatment is often toxic also to the
cells of our body Parasites
- we cannot vaccinate against these Size Highly variable: tiny protozoa (5-10 μm) to
type of pathogens large tapeworms (1 m)
Structure Eukaryotes; unicellular (protozoa) or
4. Parasites multicellular (e.g. worms)
- we usually do not have problems Lifestyle Complex and highly variable
with parasites, but large parts of the Pathogenesis Complex and highly variable; very high
world have prevalence (2.5 billion infected)
Treatment Possible but difficult due to toxicity
Prevention Hygiene, prophylaxis (malaria)
Relation between pathogen and disease
- one single pathogen can cause a range of
different diseases
- endocarditis is an infection of the heart
muscle
- one disease (e.g. common cold) can be
caused by a range of different pathogens (200
different virus species which can cause
common cold symptoms)

,#SHORT INTRODUCTION TO EPIDEMIOLOGY

Exposure = infection = disease?
- at any given moment we carry many different potentially pathogenic microbes: pathogens that just
entered our body, or microorganisms that usually live with us in peace, but can cause problems when
they are in the wrong place
- only a minority of exposures leads to infection
- most infections are controlled by innate immunity and remain subclinical
- the % of clinically apparent infections depends on:
the susceptibility of the host (condition of the host)
the microbe (hepatitis A 90% asymptomatic, measles virus 99% symptomatic)
- pathogens differ enormously in how often they cause symptomatic disease
- overall the infections we see as clinical are only the tip of the iceberg

Prevalence: (total) number of infected (with a certain pathogen) individuals at a
given time
- depends on number of new infections, duration of disease and loss due to death
(or recovery)
Incidence: number of new infections in a given time period
Recurrence: number of infected which get reinfected
Mortality: number of infected lost due to death

Phases of an infectious disease
- incubation period: the time interval between the
actual infection and the moment that clinical signs
appear (can be short (common cold, 1-2 days) or
very long (HIV infection, years)
- often the disease symptoms that are
characteristic of a particular infection are preceded
by aspecific symptoms
- prodome / prodomal phase: the period of
aspecific symptoms
- latent phase: early after infection, not infectious
- infectious: patient starts to transmit the pathogen
→ can be before any symptoms appear or before the specific symptoms appear → subclinically
infectious (impossible to prevent spread of the infection by isolating symptomatic patients)

Factors determining infectiousness
- the infectious agent: time between infection of a person and becoming infectious
- duration of infectiousness
- the probability of transmission given a contact between an infectious person and a susceptible
person
- the environment: the type of contacts between infectious and susceptible individuals
the number of contacts
- the characteristics of the individuals in the population:
- susceptibility of the population (number of susceptible individuals and degree of
susceptibility)
- infectiousness of the infected person (e.g. superspreader or not)

,Serial interval: time interval between onset of clinical symptoms between two cases
- determined by the length of the incubation time and the infectious period
- infection control if the serial interval is shorter than the incubation time: it becomes more difficult,
because people are spreading the infection before they know that they are sick




Duration time: time it takes for number of cases to double →
exponential growth
- the duration time can vary a lot
- depends on the incubation time of the infection or on the serial interval
- a city’s health care system can handle about one thousand case if all
resources are mobilized → if the doubling time is 2 days, the authorities
are given only 20 days to have everything in place

Development of SARS-CoV-2 epidemic in NL (spring 2020)
- curve starts to flatten earlier in logarithmic scale (exponentional growth
is red straight line) than in linear scale

Basic reproduction number R0: average number of infected individuals produced by one infected
case (number can vary greatly)
- it is important that the R0 of an infectious disease is reduced to below 1, because then one person
does infect less than one other person and the infection will die out

, #HEADS UP IN BACTERIOLOGY

Alexander Fleming (1881-1955): discovered antibiotics
Edward Jenner (1749-1823)r: discovered vaccination with cowpox
Robert Koch (1843-1910): discovered the tubercle bacterium (which causes tuberculosis)
Antoni van Leeuwenhoek (1632-1723): discovered the microscope
Louis Pasteur (1822-1895): discovered that microorganisms do not develop spontaneously; he used a
technique to pasteurize, sterilize products
Marshall & Warren (2005): got a nobel prize for their
discovery of the Helicobacter bacterium

Tree of life: defined 20/30 years ago
- common ancestor
- red lines (branches) contain pathogens that might be
dangerous for us → genera with pathogens
- biological definition of ‘life’:
1. Independent metabolism
2. Independent replication
- human bacterial microbiota: 500 à 1000 species / ~ 1014 cells

Major features of pro- and eukaryotes
1. Prokaryotes
- have a very simple make-up
- do not have a nucleus
- unicellular microorganisms
- have a cell wall
- have little ribosomes in the cytoplasm
- have DNA in the middle of the cell
- also loose plasmids might be present there

2. Eukaryotes
- have cell organelles and have a nucleus
- mitochondria and chloroplasts are coming from bacteria that were
engulfed by some kind of prokaryotic cell that took up these bacteria
or archaea and made them into mitochondria (and chloroplasts)
- mitochondria have their own ribosomal RNA as well → prokaryotic
cell within an eukaryotic cell
- our endoplasmic reticulum (membrane system) contains the
ribosomes → especially in the rough endoplasmic reticulum

Gram stain morphology of bacteria
- identify by recognition of two kinds of bacterial cell walls → makes it easy to classify the bacteria
- gram positive cell wall: made up out of one membrane with on top a whole thick layer of
peptidoglycan cell wall mixed with teichoic acid and lipoteichoic acid → this particular peptidoglycan
can be stained by crystal violet gram staining → stains all bacteria purple, and is fixed by iodine and
then if you decolorize by alcohol or acetone then either the color gets lost (in Gram negative
bacteria) or the color remains (then you have a Gram positive bacteria; color gets stuck in the
peptidoglycan layer)
- safranin red or fuchsine stain the bacteria red or reddish or pinkish
- Gram negative don’t retain the Gram (crystal violet) stain, because they don’t have this

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